Hydrocortisone Plus Fludrocortisone in High-risk Patients Undergoing for Cardiac Surgery

Обзор

Cardiac surgery is a high-risk surgery and is associated with a rate of postoperative adverse outcomes. Like many others major surgery, cardiac surgery procedures induce a proinflammatory phase usually counterbalanced with an immunosuppressive phase so the immune response remained balanced. In some cases, the immune response might be dysregulated with a more pronounced pro inflammatory state that compromises organ perfusion and with the occurrence of organ failure. From a mechanistic approach, the relationship between organ failure is complex and multifactorial with a high level of proinflammatory cytokines, a decrease in microcirculation, an endothelial dysfunction and an activation of coagulation and over. The clinical expression is an increase in vasopressor exposure and dose, an increase in mortality and in adverse outcomes with a predominance of acute kidney injury. Various therapies have been assessed to manage cardiac surgery related sepsis including glucocorticoid therapy. Briefly, two major randomized trials assessed glucocorticoid therapy solely in scheduled cardiac surgery with cardiopulmonary bypass. No clinical benefit was demonstrated in term of reduction in postoperative mortality or adverse outcomes. Since, data support that the selection of patients at risk is crucial to demonstrate such a strategy. Indeed, data support that surprisingly some patients will have a very light immune response reflected by a low pro inflammatory cytokine. The hypothesis is that the combination glucocorticoid and fludrocortisone could decrease adverse outcomes in selected patients.

Вмешательства

• Препарат hydrocortisone plus fludrocortisone
  * Hydrocortisone 200 mg/day for 5 days or until ICU discharge, starting at the initiation of cardiopulmonary bypass (CPB), administered intravenously via syringe pump in a double-blind manner * Fludrocortisone 50 µg/day in the morning for 5 days or until ICU discharge, administered orally or via nasogastric tube (if the patient is sedated), diluted in a glass of water, in a double-blind manner
• Препарат placebo of hydrocortisone plus fludrocortisone
  * Placebo for hydrocortisone (0.9% NaCl) administered following the same protocol as fludrocortisone in the intervention group * Placebo for fludrocortisone (capsule containing microcrystalline cellulose diluted in a glass of water) administered following the same protocol as fludrocortisone in the intervention group

Первичные конечные точки

• Variation of acute kidney injury occurence between both groups [Срок оценки: up to 7 days]
• Variation of postoperative pulmonary complication occurrence between both groups [Срок оценки: up to 7 days]
• Variation of number of norepinephrine requirement between both groups [Срок оценки: up to 7 days]

Вторичные конечные точки (6)

• variation of postoperative atrial fibrillation occurence between both groups [Срок оценки: up to 7 days]
• variation of myocardial infarction occurence between both groups [Срок оценки: up to 7 days]
• variation of stroke occurence between both groups [Срок оценки: up to 7 days]
• Variation of total amount of norepinephrine between both groups [Срок оценки: up to 7 days]
• variation of occurrence of glucocorticoid side effect between both groups [Срок оценки: up to 7 days]
• Variation of 28-day mortality between both groups [Срок оценки: at 28 days]

Критерии участия

Критерии включения

• Age > 18 years.
• Patient at intermediate/high risk (EuroSCORE II > 4%).
• Patient admitted for scheduled cardiac surgery:

• Coronary artery bypass grafting (CABG).
• Aortic valve replacement.
• Mitral valve repair or replacement.
• Surgery of the aortic root (aortic tube, Bentall procedure, Tirone David procedure, or other).
• Combined surgery.
• Patient undergoing cardiopulmonary bypass (CPB).
• Informed consent signed by the patient.

Критерии исключения

• Endocarditis
• Off-pump heart surgery
• Heart transplantation or long-term ventricular assist device (VAD)
• Emergency surgery: aortic dissection, emergency coronary artery bypass grafting (CABG)
• Failure to wean from CPB requiring short-term mechanical support (intra-aortic balloon pump, ECMO)
• Hypothermic surgery
• History of cardiac surgery
• Patient on long-term corticosteroid therapy
• Autoimmune disease or chronic inflammatory condition
• End-stage renal disease on long-term dialysis
• Contraindications to the administration of hydrocortisone and/or fludrocortisone according to the summary of product characteristics (SmPC)
• Pregnant or breastfeeding woman
• Patient under legal protection (guardianship, curators, or judicial safeguard).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• CHRU Amiens — Amiens

Идентификаторы

NCT: NCT07037043 · PI2024_843_0047

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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